ASBMR: Old Idea for Keeping Osteoporosis in Check Gets New Airing

Action Points

Explain to interested patients that one treatment for osteoporosis is injections of a form of parathyroid hormone, which triggers bone-building.

Note that these studies report on early trials of compounds aimed at inducing the body to produce its own pulse of parathyroid hormone, but caution more research remains.

Note that these studies were published as abstracts and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

MONTREAL, Sept. 16 -- Compounds are starting to be seen on the horizon that induce the body to treat itself for osteoporosis with a burst of endogenous parathyroid hormone.

In successive presentations at the American Society for Bone and Mineral Research meeting here, researchers described early studies on two novel molecules -- dubbed calcilytics -- that would block the parathyroid calcium sensing receptor.

The result of such a blockade is a pulse of parathyroid hormone that triggers its anabolic bone-building properties, said John Bilezikian, M.D., of Columbia University, a former society president who was not involved in the research.

The idea has been around for a while and it's "very attractive" for at least three reasons, Dr. Bilezikian said:

The released parathyroid hormone would be the natural substance. "You're pulsing the real stuff," he said.

The parathyroid drugs, such as teriparatide (Forteo), are expensive -- up to $8,000 a year -- and are given by injection.

And teriparatide, because of an early report of osteosarcoma in rats, carries a black box warning, which is worrisome to some clinicians and patients although human cases are extremely rare.

On the other hand, he noted, the molecules reported here are still in early trials.

Ronacaleret was tested in 81 postmenopausal women who were divided into three dose cohorts -- 75, 175, or 475 mg -- as well as a placebo group, according to Lorraine Fitzpatrick, M.D., of GlaxoSmithKline in Collegeville, Pa.

The endpoints were safety and tolerability, as well as change in a range of bone turnover markers over a 28-day test period.

The drug was well tolerated, Dr. Fitzpatrick said, with adverse events mostly mild or moderate. One volunteer met pre-defined criteria for elevations in serum calcium and was withdrawn, but had no symptoms.

The researchers also found a dose-dependent increase in bone formation markers. For instance, for the highest dose, the mean changes from baseline of osteocalcin, type I procollagen, and bone-specific alkaline phosphatase were 63%, 79%, and 35%, respectively, differences significant at P<0.05 relative to placebo.

At the same time, carboxy-terminal collagen crosslinks -- a marker of bone resorption -- did not change significantly.

The other presentation highlighted a safety study of another calcylitic compound called ATF936 in 14 healthy men whose mean age was 33, according to Leo Widler, Ph.D., of the Novartis Institutes of Biomedical Research in Basel, Switzerland.

Like ronacaleret, it caused a transient spike in serum parathyroid hormone whose height was dependent on dose. The profile of the spike was similar with that seen with teriparatide, Dr. Wilder said.

The drug was well tolerated, he said, and there were "no safety concerns." The researchers did not measure bone turnover markers.

"The real challenge," Dr. Bilezikian said, "is to get a drug that will truly give an endogenous pulse."

The data presented here for both compounds show a "quick hit" but Dr. Bilezikian said it's not clear how quickly the parathyroid hormone levels return to normal.

If they remain elevated for any length of time, he said, patients will suffer drug-induced hyperparathyroidism.

The osteoporosis research community has been "thinking about this for years," Dr. Bilezikian said, with occasional research presentations that did not lead to products.

"It's great to see this at this meeting, however," he said, adding, "It's a work in progress."

The study of ronacaleret was sponsored by GlaxoSmithKline. Dr. Fitzpatrick is an employee of the company.

The study of ATF936 was sponsored by Novartis. Dr. Widler is an employee of the company.

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